There are an estimated 26 million Americans with early chronic kidney disease (CKD). Early diagnosis and treatment are the only cost-effective means to reverse this growing problem. NIH recognizes the challenge to diagnose CKD early during its initiation and development phases in order to prevent further renal damage, reduce cardiovascular risk, and minimize the economic impact of CKD. Current methods and biomarkers that are used to assess CKD are effective once the disease is well established but are not reliable for the detection of early disease. Further, many patients initially determined to have a mild decline in kidney function by the current methods may actually be misclassified and possibly under-diagnosed, resulting in a patient having undiagnosed moderate to severe kidney damage. We will produce a new ELISA for CKD to be employed as a diagnostic test based upon the use of a novel biomarker that reflects early events in the pathophysiology of kidney disease. Detection of this biomarker for CKD will give laboratory results and clinical insight that are complementary to creatinine-based glomerular filtration rate (GFR) estimates as well as tests for urine albumin. This should result is a more reliable and earlier identification of CKD. n addition, our CKD-Assay would give physicians the ability to evaluate patients that have been recently diagnosed with hypertension or diabetes. In Phase I, we evaluated the feasibility and proof-of principal of this test and found that the prototype assay in both populations was highly sensitive and specific. In Phase II, we will look for the influence of comorbid conditions and medications on assay performance, compare our results to the gold standard assay of GFR, and follow up patients over at least 3 years to evaluate the ability of this biomarker to follow progression of CKD. Lastly, we will evaluate whether patient characteristics such as age, gender, BMI, ethnicity, and other factors impact on assay performance. We request Phase II support so that we can evaluate the prototype assay and further test its feasibility to help identiy at-risk patients for early kidney disease and monitor therapy with the ultimate goal of obtaining FDA approval and reducing the societal impact of under-diagnosed CKD. PUBLIC HEALTH RELEVANCE: Chronic Kidney Disease affects nearly 26 million people in the United States, which places them at higher risk of cardiovascular disease and hemodialysis. We will develop an assay for the identification of people with advanced kidney disease that are under-diagnosed by current methods and to aid physicians in earlier treatment and better assessment of chronic kidney disease.